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The role of large-conductance, calcium-activated potassium channels in a rat model of trigeminal neuropathic pain.
Cephalalgia 2015; 35(1):16-35C

Abstract

BACKGROUND

Trigeminal neuralgia is a disorder of paroxysmal and severely disabling facial pain and continues to be a real therapeutic challenge. At present there are few effective drugs. Here the aim of this study was to investigate the role of BKCa channels in trigeminal neuropathic pain.

METHODS

Rats were divided into two groups: a sham and a chronic constriction injury of infraorbital branch of trigeminal nerve (ION-CCI) group. Nociceptive behavior testing, immunohistochemistry, RT-PCR, Western blotting and whole-cell patch clamp recording were used.

RESULTS

Relative to the sham group, rats with ION-CCI consistently displayed lower mechanical pain thresholds in the vibrissal pad region from day 6 to 42 after ION-CCI operation. ION-CCI induced a significant down-regulation of BKCa channels both in mRNA and protein levels in the ipsilateral trigeminal ganglion (TG), a lower threshold intensity of action potential, and decreased total BKCa currents in cultured TG neurons. TG target injection of NS1619 (20-100 µg), an opener of BKCa channels, dose-dependently increased the mechanical pain threshold, which was blocked by the BKCa channel inhibitor iberiotoxin (IbTX, 20 µg). NS1619 (10 µM) significantly increased the mean threshold intensities of action potentials in ION-CCI rats, while failing to affect those in the sham rats. The levels of phosphorylated extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinases (JNK) in TG were significantly increased after ION-CCI operation. The ERK1/2 antagonist U0126, p38 antagonist SB203580 and JNK antagonist SP600125 significantly reversed the facial mechanical allodynia in ION-CCI rats. However, the ERK1/2 antagonist U0126, p38 antagonist SB203580 but not JNK antagonist SP600125 significantly increased BKCa currents in ION-CCI TG neurons.

CONCLUSIONS

Our results indicate the important involvement of mainly ERK and p38 MAPK pathways in modulating BKCa channels in ION-CCI TG neurons. BKCa channels represent a new therapeutic target for the clinical treatment of trigeminal neuropathic pain.

Authors+Show Affiliations

Department of Physiology and Key Laboratory of Molecular Neurobiology, Ministry of Education, Second Military Medical University, PR China Department of Stomatology, Changzheng Hospital, Second Military Medical University, PR China.Department of Physiology and Key Laboratory of Molecular Neurobiology, Ministry of Education, Second Military Medical University, PR China.Department of Physiology and Key Laboratory of Molecular Neurobiology, Ministry of Education, Second Military Medical University, PR China Department of Anesthesia, Changhai Hospital, Second Military Medical University, PR China.Department of Physiology and Key Laboratory of Molecular Neurobiology, Ministry of Education, Second Military Medical University, PR China.Department of Stomatology, Changzheng Hospital, Second Military Medical University, PR China.Department of Physiology and Key Laboratory of Molecular Neurobiology, Ministry of Education, Second Military Medical University, PR China mabei08@aliyun.com zhaoyf1818@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24820887

Citation

Liu, Cai-Yue, et al. "The Role of Large-conductance, Calcium-activated Potassium Channels in a Rat Model of Trigeminal Neuropathic Pain." Cephalalgia : an International Journal of Headache, vol. 35, no. 1, 2015, pp. 16-35.
Liu CY, Lu ZY, Li N, et al. The role of large-conductance, calcium-activated potassium channels in a rat model of trigeminal neuropathic pain. Cephalalgia. 2015;35(1):16-35.
Liu, C. Y., Lu, Z. Y., Li, N., Yu, L. H., Zhao, Y. F., & Ma, B. (2015). The role of large-conductance, calcium-activated potassium channels in a rat model of trigeminal neuropathic pain. Cephalalgia : an International Journal of Headache, 35(1), pp. 16-35. doi:10.1177/0333102414534083.
Liu CY, et al. The Role of Large-conductance, Calcium-activated Potassium Channels in a Rat Model of Trigeminal Neuropathic Pain. Cephalalgia. 2015;35(1):16-35. PubMed PMID: 24820887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of large-conductance, calcium-activated potassium channels in a rat model of trigeminal neuropathic pain. AU - Liu,Cai-Yue, AU - Lu,Zhan-Ying, AU - Li,Na, AU - Yu,Li-Hua, AU - Zhao,Yun-Fu, AU - Ma,Bei, Y1 - 2014/05/12/ PY - 2014/5/14/entrez PY - 2014/5/14/pubmed PY - 2015/8/12/medline KW - BKCa channel KW - ERK KW - JNK KW - chronic constriction injury (CCI) KW - mitogen-activated protein kinase (MAPK) KW - p38 KW - trigeminal neuropathic pain SP - 16 EP - 35 JF - Cephalalgia : an international journal of headache JO - Cephalalgia VL - 35 IS - 1 N2 - BACKGROUND: Trigeminal neuralgia is a disorder of paroxysmal and severely disabling facial pain and continues to be a real therapeutic challenge. At present there are few effective drugs. Here the aim of this study was to investigate the role of BKCa channels in trigeminal neuropathic pain. METHODS: Rats were divided into two groups: a sham and a chronic constriction injury of infraorbital branch of trigeminal nerve (ION-CCI) group. Nociceptive behavior testing, immunohistochemistry, RT-PCR, Western blotting and whole-cell patch clamp recording were used. RESULTS: Relative to the sham group, rats with ION-CCI consistently displayed lower mechanical pain thresholds in the vibrissal pad region from day 6 to 42 after ION-CCI operation. ION-CCI induced a significant down-regulation of BKCa channels both in mRNA and protein levels in the ipsilateral trigeminal ganglion (TG), a lower threshold intensity of action potential, and decreased total BKCa currents in cultured TG neurons. TG target injection of NS1619 (20-100 µg), an opener of BKCa channels, dose-dependently increased the mechanical pain threshold, which was blocked by the BKCa channel inhibitor iberiotoxin (IbTX, 20 µg). NS1619 (10 µM) significantly increased the mean threshold intensities of action potentials in ION-CCI rats, while failing to affect those in the sham rats. The levels of phosphorylated extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinases (JNK) in TG were significantly increased after ION-CCI operation. The ERK1/2 antagonist U0126, p38 antagonist SB203580 and JNK antagonist SP600125 significantly reversed the facial mechanical allodynia in ION-CCI rats. However, the ERK1/2 antagonist U0126, p38 antagonist SB203580 but not JNK antagonist SP600125 significantly increased BKCa currents in ION-CCI TG neurons. CONCLUSIONS: Our results indicate the important involvement of mainly ERK and p38 MAPK pathways in modulating BKCa channels in ION-CCI TG neurons. BKCa channels represent a new therapeutic target for the clinical treatment of trigeminal neuropathic pain. SN - 1468-2982 UR - https://www.unboundmedicine.com/medline/citation/24820887/The_role_of_large_conductance_calcium_activated_potassium_channels_in_a_rat_model_of_trigeminal_neuropathic_pain_ L2 - http://journals.sagepub.com/doi/full/10.1177/0333102414534083?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -